5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.

中文翻译：

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无严重毒性生存：急性淋巴细胞白血病后不可接受的长期毒性的医生定义。

儿童急性淋巴细胞白血病的 5 年总生存率已超过 90%，但幸存者面临永久性健康后遗症的风险。尽管无事件生存率恰当地代表了总体生存率较差的癌症的结果，但当治愈率很高但受到严重、持续性并发症的挑战时，该指标是不够的。因此，代表 17 个国际急性淋巴细胞白血病研究组的一组儿科血液肿瘤学专家发起了一项倡议，以构建一个名为严重无毒性生存 (STFS) 的措施，以量化医生优先考虑的毒性的发生与标准的癌症结果报告相结合。五个通用纳入标准（在癌症诊断前不存在、有症状、客观、严重程度不可接受、永久性、或需要不可接受的治疗）被用来评估 855 种健康状况，其中包括 21 种严重毒性。共识定义是通过修改后的 Delphi 流程达成的，并辅以两次额外的全体会议。这 21 种严重毒性包括严重影响日常生活活动且对治疗无效（例如，顽固性癫痫发作）、没有治疗选择（例如，失明）或需要大量侵入性治疗（例如，心脏移植）的严重不良健康状况。将 STFS 评估纳入临床试验有可能改善和多样化治疗策略，不仅关注传统的结果事件和总生存期，还关注最严重毒性的频率。本次审查的两个主要目标是：优先考虑并定义儿童急性淋巴细胞白血病患者不可接受的长期毒性，并定义如何将这些毒性组合成一个复合量，以与其他报告的结果相结合。尽管 STFS 使用儿童急性淋巴细胞白血病作为模型疾病量化了临床上不可接受的健康权衡，但优先考虑的严重毒性是基于与任何其他癌症诊断和年龄组相关的一般考虑。